This invention generally provides coated potassium chloride granules that may be used to make extended release potassium chloride tablets. Specifically, the present invention provides ethylcellulose-coated crystals of potassium chloride that may be orally administered to a patient requiring potassium supplementation. The coated potassium chloride granules provide extended release of the potassium chloride in the gastrointestinal tract that results in substantially less irritation to the gastric mucosa.
The administration of many diuretics, commonly used to treat patients having hypertension, increases the excretion of both sodium and potassium. The acute administration of such diuretics to a patient normally causes no problems. However, chronic administration of diuretics to some patients can result in the depletion of potassium from the patient, a condition known as hypokalemia. Potassium depletion may be accompanied by a reduced tolerance to carbohydrates and a deficiency in glycogen deposition. Further, vasopressin-resistant polyuria is another complication. A deficit of potassium also appears to increase the renal synthesis of prostaglandins, which in turn can decrease the permeability to water of the distal nephron and produce a diabetes insipidus-like syndrome.
In order to avoid these complications, supplemental potassium administration is typically needed. When potassium is taken along with a normal diet it is slowly absorbed from the intestinal tract. Following potassium distribution and uptake by the cells, the kidneys excrete an appropriate amount to maintain a proper balance. As a consequence of a large volume of distribution and a rapid response of the kidney, the extracellular and intracellular concentrations of potassium are normally maintained within relatively narrow limits.
When potassium is administrated as a drug, the factors that govern the rate and extent of its distribution are of major importance. It is not possible to increase the total cellular content of potassium significantly above normal. However, it is very easy to raise the extracellular concentration excessively. It is the concentration of potassium in the extracellular fluid that determines life-threatening toxicity.
It is well known that large doses of potassium chloride taken orally can cause gastrointestinal irritation, purging, weakness and circulatory disturbances. Since potassium depletion can cause problems for the patient, a controlled or extended release formulation of potassium chloride that replenishes potassium in an acceptable manner without undesirable side effects is desired.
In an attempt to meet the need for suitable formulations that may be used as a potassium supplement, a number of different dosage formulations have been developed. U.S. Pat. No. 4,352,791 reports a composition of potassium and a therapeutically acceptable salicylate salt of salicylic acid. U.S. Pat. No. 4,340,582 reports an enteric coated tablet that may include potassium chloride. U.S. Pat. No. 4,259,323 reports a potassium chloride emulsion. U.S. Pat. No. 4,259,315 reports a controlled release potassium dosage from gelatin capsules that contain a mixture of ethylcellulose-encapsulated potassium chloride and a hydrophilic surfactant. Film-coated tablets containing potassium chloride in a wax matrix (non-enteric coated) are marketed as a slowly available potassium source. U.S. Pat. No. 4,235,870 reports a slow release pharmaceutical composition of a combination of higher aliphatic alcohols and hydrated hydroxyalkyl cellulose. U.S. Pat. No. 4,863,743 reports a controlled release potassium chloride tablet made of potassium chloride crystals coated with higher molecular weight (measured viscosity greater than 40 cP in toluene/ethanol) ethylcellulose and hydroxypropylcellulose. U.S. Pat. No. 5,397,574 reports controlled release potassium chloride micropellets coated with lower molecular weight (measured viscosity less than 10 cP in toluene/ethanol) ethylcellulose and a plasticizer.